Research & Scholarship

Current Research and Scholarly Interests

My research group focuses on the diagnosis and treatment of cardiovascular emergencies including acute myocardial infarction, acute coronary syndrome and congestive heart failure. We have evaluated a number of novel cardiac markers and point-of-care testing in clinical practice. Current projects also include the diagnosis and treatment of acute pulmonary embolism and deep venous thrombosis.

This pilot phase II trial studies how well giving brentuximab vedotin, combination
chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB
or IV Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer
growth in different ways. Some block the ability of cancer to grow and spread. Others find
cancer cells and help kill them or carry cancer killing substances to them. Drugs used in
chemotherapy, such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide,
and dacarbazine, work in different ways to stop the growth of cancer cells, either by
killing the cells or by stopping them from dividing. Radiation therapy uses high-energy
x-rays to kill cancer cells. Giving brentuximab vedotin with combination chemotherapy may
kill more cancer cells and reduce the need for radiation therapy.

This pilot study will primarily be evaluated by feasibility and adherence to an iPad-based
neurocognitive intervention program. It will secondarily be evaluated by performance on the
neurocognitive testing post-transplant and change in performance in subsequent years.

The purpose of this study is to determine if the use of adjunctive Pharmacomechanical
Catheter Directed Thrombolysis, which includes the intrathrombus administration of
rt-PA--Activase (Alteplase),can prevent the post-thrombotic syndrome(PTS)in patients with
symptomatic proximal deep vein thrombosis(DVT)as compared with optimal standard DVT therapy
alone.

Abstract

Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE).This was a subanalysis of the CHOPIN study, a 16-center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6-month all-cause mortality and the secondary endpoint was 30-day and 6-month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure.MR-proADM performed similarly to troponin (cTnI; c-statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR-proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6-month mortality risk versus 0.9% risk for those in the bottom nine deciles (p

Abstract

Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain.MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data.From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative.High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Abstract

Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome.This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes.The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE.A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort.For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.

Abstract

Many emergency department (ED) patients have symptoms that may be attributed to arrhythmias, necessitating outpatient ambulatory cardiac monitoring. Consensus is lacking on the optimal duration of monitoring. We describe the use of a novel device applied at ED discharge that provides continuous prolonged cardiac monitoring.We enrolled discharged adult ED patients with symptoms of possible cardiac arrhythmia. A novel, single use continuous recording patch (Zio®Patch) was applied at ED discharge. Patients wore the device for up to 14 days or until they had symptoms to trigger an event. They then returned the device by mail for interpretation. Significant arrhythmias are defined as: ventricular tachycardia (VT) ≥4 beats, supraventricular tachycardia (SVT) ≥4 beats, atrial fibrillation, ≥3 second pause, 2nd degree Mobitz II, 3rd degree AV Block, or symptomatic bradycardia.There were 174 patients were enrolled and all mailed back their devices. The average age was 52.2 (± 21.0) years, and 55% were female. The most common indications for device placement were palpitations 44.8%, syncope 24.1% and dizziness 6.3%. Eighty-three patients (47.7%) had ≥1 arrhythmias and 17 (9.8%) were symptomatic at the time of their arrhythmia. Median time to first arrhythmia was 1.0 days (IQR 0.2-2.8) and median time to first symptomatic arrhythmia was 1.5 days (IQR 0.4-6.7). 93 (53.4%) of symptomatic patients did not have any arrhythmia during their triggered events. The overall diagnostic yield was 63.2%The Zio®Patch cardiac monitoring device can efficiently characterize symptomatic patients without significant arrhythmia and has a higher diagnostic yield for arrhythmias than traditional 24-48 hour Holter monitoring. It allows for longer term monitoring up to 14 days.

Abstract

The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED).Copeptin is secreted from the pituitary early in the course of AMI.This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99 th percentile 40 ng/l; 10% coefficient of variation 0.03 μg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results.AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001).Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws.

Abstract

We evaluated a third-generation high sensitivity "guidelines acceptable" troponin I assay (hs-cTnI) against a contemporary "clinically usable" troponin assay (cTnI).Remnant samples of undifferentiated emergency department (ED) patients with suspected acute coronary syndrome were enrolled. Baseline and 90-minute samples were analyzed for cTnI and hs-cTnI. Sensitivity, specificity, positive and negative predictive values for AMI and 30-day adverse cardiac events (ACE) were compared.Of 486 ED patients, there were 465 patients who had blood remaining at the presentation for the hs-cTnI assays, with 12 AMIs. At presentation, the clinical sensitivity and specificity for AMI was 75% and 97% for cTnI and 83.3 and 82.1% for hs-cTnI. There were 407 patients who had paired baseline and 90-minute blood samples for cTnI and hs-cTnI including 9 of the 12 AMI patients. The sensitivity and specificity was 77.7% and 96.5% for cTnI and 100% and 81.9% for hs-cTnI at 90 min. A ? change of 30% increase from baseline to 90 min improved the specificity to 94.5% (95% CI 92%-96%) without lowering the sensitivity. When AMI was defined as a ?30% change of hs-cTnI at t=0 and 90 min and one hs-cTnI result >99th percentile cutoff, more than 3 times as many patients met the diagnostic criteria for AMI compared to results from the normal sensitive troponin assay; 28 (6.9%) for hs-cTnI vs. 9 (2.2%) with cTnI. There were 37 in-hospital or 30-day events, producing an OR of 3.03, 95% CI: 0.86-9.59 for cTnI, and 2.54, 95% CI: 1.27-5.10 for hs-cTnI, which detected 11 more cases.The hs-cTnI assay achieved a 90-minute rule out for AMI and detected more 3 times as many AMI cases. The specificity increased with the ?30% criteria. The hs-cTnI assay also detected more cases of patient at risk for adverse cardiac events at 30 days.

Abstract

In a large U.S. sample, this study measured the presentation features, testing, treatment strategies, and outcomes of patients diagnosed with pulmonary embolism (PE) in the emergency department (ED).No data have quantified the demographics, clinical features, management, and outcomes of outpatients diagnosed with PE in the ED in a large, multicenter U.S. study.Patients of any hemodynamic status were enrolled from the ED after confirmed acute PE or with a high clinical suspicion prompting anticoagulation before imaging for PE. Exclusions were inability to provide informed consent (where required) or unavailability for follow-up.A total of 1,880 patients with confirmed acute PE were enrolled from 22 U.S. EDs. Diagnosis of PE was based upon positive results of computerized tomographic pulmonary angiogram in most cases (n = 1,654 [88%]). Patients represented both sexes equally, and racial and ethnic composition paralleled the overall U.S. ED population. Most (79%) patients with PE were employed, and one-third were older than age 65 years. The mortality rate directly attributed to PE was 20 in 1,880 (1%; 95% confidence interval [CI]: 0% to 1.6%). Mortality from hemorrhage was 0.2%, and the all-cause 30-day mortality rate was 5.4% (95% CI: 4.4% to 6.6%). Only 3 of 20 patients with major PE that ultimately proved fatal had systemic anticoagulation initiated before diagnostic confirmation, and another 3 of these 20 received a fibrinolytic agent.Patients diagnosed with acute PE in U.S. EDs have high functional status, and their mortality rate is low. These registry data suggest that appropriate initial medical management of ED patients with severe PE with anticoagulation is poorly standardized and indicate a need for research to determine the appropriate threshold for empiric treatment when PE is suspected before diagnostic confirmation.

Abstract

Point-of-care testing reduces time to cardiac marker results in patients evaluated for acute coronary syndromes, yet evidence this translates to a decreased length of stay is lacking. We hypothesized that point-of-care testing decreases length of stay in patients being evaluated for acute coronary syndromes in the emergency department (ED).Patients being evaluated for possible acute coronary syndromes at 4 EDs in the United States were randomized to having point-of-care markers as well as central laboratory markers, or central laboratory markers only (laboratory arm). Point-of-care markers were obtained using early serial testing at presentation and at 90, 180, and 360 minutes as required by the treating physician. Evaluation, treatment, and disposition decisions were at the treating physician's discretion. Length of stay was from presentation to the time of departure from the ED, either to an inpatient setting or to home.There were 1,000 patients in each study arm. There were 520 patients discharged home from the ED. Median (interquartile range) time to discharge home was 4.6 hours (3.5 to 6.1 hours) in laboratory patients and 4.5 hours (3.5 to 6.1 hours) in point-of-care patients. Median (interquartile range) time to transfer to an inpatient setting for admitted patients was 5.5 hours (4.2 to 7.5 hours) in laboratory patients, and 5.4 hours (4.1 to 7.3 hours) in point-of-care patients. At one site, time to transfer to the floor was reduced in the point-of-care arm compared with the laboratory arm (difference in medians 0.45 hours; 95% confidence interval [CI] -0.14 to 1.04 hours). At one site, time to ED departure for discharged patients was higher in the point-of-care arm than the laboratory arm (difference in medians 1.25 hours; 95% CI 0.13 to 2.36 hours).The effect of point-of-care testing on length of stay in the ED varies between settings. At one site, point-of-care testing decreased time to admission, whereas at another, point-of-care testing increased time to discharge. Potential effects of point-of-care testing on patient throughput should be considered in the full context of ED operations.

Abstract

Our purpose was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure and baseline renal dysfunction.Although nesiritide is approved for the treatment of acute decompensated heart failure, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue.Consecutive patients with acute decompensated heart failure and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive nesiritide (0.01 microg/kg/min with or without a 2-microg/kg bolus) or placebo (5% dextrose in water) for 48 h in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by > or =20% and change in serum creatinine.Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs. 75.5 years, respectively), blood pressure (123/64 vs. 125/64 mm Hg) and serum creatinine (1.82 vs. 1.86 mg/dl). There were no significant differences in the incidence of a 20% creatinine rise (23% vs. 25%) or in the change in serum creatinine (-0.05 vs. +0.05 mg/dl). There were no significant differences in the secondary end points of change in weight (-2.19 vs. -1.58 kg), intravenous furosemide (125 vs. 107 mg), discontinuation of the infusion due to hypotension (13% vs. 6%), or 30-day death/hospital readmission (33% vs. 25%).In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with acute decompensated heart failure. (BNP-CARDS trial; http://www.clinicaltrials.gov/ct/show/NCT00186329?order=1; NCT00186329).

Abstract

Simvastatin and other HMG-CoA reductase inhibitors (statins) are one of the most frequently prescribed class of medications in the United States, with over 15 million Americans taking these drugs. Relatively rare adverse effects related to the known toxic effects of these drugs are more common than generally realized. Clinically significant statin-induced rhabdomyolysis is an uncommon but life-threatening adverse effect. We describe a case of simvastatin-induced rhabdomyolysis. Current knowledge of the pharmacology of the HMG-CoA reductase inhibitors and the drug interactions that potentiate these adverse effects are discussed. The clinical features of rhabdomyolysis and current treatment recommendations are presented.

Abstract

Amiodarone is currently indicated for the treatment of life-threatening ventricular dysrhythmias. It is also used for the treatment of supraventricular dysrhythmias and as maintenance therapy after successful cardioversion of atrial flutter or atrial fibrillation. Adverse effects related to its expanded use are increasingly common. We describe a case of amiodarone-induced thyrotoxicosis occurring 5 months after cessation of therapy and discuss the pathophysiology and treatment of this disorder.

Abstract

Given that adverse drug events result in extensive costs and healthcare resource utilization, the goal is to better understand drug-related emergency department (ED) visits so that programs can be implemented to improve the quality of health care.To (1) determine the incidence of drug-related ED visits at a large, tertiary care, Veterans Affairs hospital; (2) identify causes of these drug-related ED visits; (3) determine patient outcomes, healthcare resource utilization, and costs associated with these visits; and (4) determine the proportion of adverse drug reaction (ADR)-related ED visits that were spontaneously reported to the hospital's ADR reporting program.We conducted a retrospective electronic chart review of all patients who visited the ED during the second week of each month in 2003. Causes for drug-related visits were identified. ADRs in this study included side effects, drug allergies, and drug-drug interactions (DDIs) and were assessed using the Naranjo probability scale.A total of 2169 patients were included in the study. Drug-related visits accounted for 12.6% of all ED visits. The main causes of drug-related visits were ADRs and nonadherence, which accounted for 33% and 19% of drug-related visits, respectively. Only 11% of these ADRs were spontaneously reported to the hospital's ADR reporting program. Thirty-five percent of drug-related visits led to hospitalizations, which resulted in an average length of stay of 9.3 days. The institution's total cost of drug-related visits was approximately 1.5 million US dollars over 12 weeks.Many ED visits are drug related and often result in hospitalization and increased healthcare resource utilization. Only a minimal number of the ADRs resulting in ED visits are spontaneously reported to hospital ADR reporting programs.

Abstract

Hospitalization rates for asthma have been reported to be higher in males than females in children under age 15, but it is not clear whether this disparity reflects gender differences in prevalence, severity, or treatment. We performed a prospective cohort study as part of the Emergency Medicine Network. Patients aged 2-13 years who presented to the emergency department (ED) with acute asthma underwent a structured interview in the ED and another by telephone 2 weeks later. Of 1,602 patients, 61% (95% CI, 59-64%) were boys. Girls were slightly older than boys, although no material differences existed in acute presentation, chronic asthma characteristics, ED treatment, or ED course. There was no difference in admission rates for boys or girls (20% vs. 22%; P = 0.48). This finding persisted when adjusting for other factors in a multivariate logistic regression model. No sex differences were observed for relapse or ongoing exacerbation on univariate or multivariate analysis. These data suggest that asthma is not inherently more severe in boys with asthma compared to girls, and that the increased rate of hospitalizations in boys under age 13 is due to differences in prevalence, not severity.

Abstract

Previous work has suggested that platelet glycoprotein IIb/IIIa receptor blockade may confer benefit in the treatment of acute myocardial infarction. The TIGER-PA pilot trial was a single-center randomized study to evaluate the safety, feasibility, and utility of early tirofiban administration before planned primary angioplasty in patients presenting with acute myocardial infarction.A total of 100 patients presenting with acute myocardial infarction were randomized to either early administration of tirofiban in the emergency room or later administration in the catheterization laboratory. The primary outcome measures were initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion ("blush"). Thirty-day major adverse cardiac events were also assessed. Angiographic outcomes demonstrate a significant improvement in initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion when patients are given tirofiban in the emergency room before primary angioplasty. The rate of 30-day major adverse cardiac events suggests that early administration may be beneficial.This pilot study suggests that early administration of tirofiban improves angiographic outcomes and is safe and feasible in patients undergoing primary angioplasty for acute myocardial infarction.

Abstract

To evaluate the impact of the diagnostic test setting-inpatient versus outpatient-on adverse cardiac events (ACEs) after six months in emergency department (ED) patients with chest pain who were admitted to the hospital and subsequently had a negative evaluation for acute coronary syndrome (ACS).The authors retrospectively studied a consecutive sample of ED patients with chest pain over a nine-month period. All patients were admitted to the hospital and underwent negative evaluations for ACS, defined as the absence of diagnostic changes on serial electrocardiograms or cardiac markers (creatine kinase-MB and troponin T), and a negative diagnostic cardiac study. Subjects were classified according to cardiac diagnostic study setting-either inpatient or outpatient. Diagnostic testing included exercise treadmill, angiography, stress echocardiography, or stress thallium scans. Acute cardiac events at six months were defined as cardiac death, myocardial infarction, unstable angina, cardiac arrest, or emergent revascularization.The six-month rate of ACEs among 157 subjects was 14%, with 2% cardiac mortality. The outpatient group had higher ACE risk when compared with the inpatient group using multivariate logistic regression, both for the entire cohort (OR 3.5, p < 0.03) and for a subgroup excluding patients with prior coronary artery disease (OR 6.7, p < 0.05). The outpatient group included 19 of 52 (37%) noncompliant subjects who did not receive a diagnostic study.Long-term cardiac morbidity of patients after a negative ACS evaluation may be higher than previously thought. Risk of ACE is significantly higher in subjects scheduled for outpatient diagnostic tests. Inpatient diagnostic testing is justified for subjects at risk for poor compliance.

Abstract

Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ED patients who presented with acute asthma underwent a structured interview in the ED, and another by telephone 2 wk later. The study was performed at 36 EDs in 18 states. A total of 51 pregnant women and 500 nonpregnant women, age 18 to 39, were available for analysis. Pregnant women did not differ from nonpregnant women by duration of asthma symptoms (median: 0.75 versus 0.75 d, p = 0.57) or initial peak expiratory flow rate (PEFR) (51% versus 53% of predicted, p = 0.52). Despite this similarity, only 44% of pregnant women were treated with corticosteroids in the ED compared with 66% of nonpregnant women (p = 0.002). Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% CI, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids.